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Background: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. Methods: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. Results: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Foundation Against Cancer Belgium, Grant/Award Number: 2014-087

After the first successful pregnancy in a liver transplant recipient in 1978, much evidence has accumulated on the course, outcomes and management strategies of pregnancy following liver transplantation. Generally, liver transplantation restores sexual function and fertility as early as a few months after transplant. Considering that one third of all liver transplant recipients are women, that approximately one-third of them are of reproductive age (18-49 years), and that 15% of female liver transplant recipients are paediatric patients who have a >70% probability of reaching reproductive age, the issue of pregnancy after liver transplantation is rather relevant, and obstetricians, paediatricians, and transplant hepatologists ever more frequently encounter such patients. Pregnancy outcomes for both the mother and infant in liver transplant recipients are generally good, but there is an increased incidence of preterm delivery, hypertension/preeclampsia, foetal growth restriction, and gestational diabetes, which, by definition, render pregnancy in liver transplant recipients a high-risk one. In contrast, the risk of congenital anomalies and the live birth rate are comparable to those of the general population. Currently there are still no robust guidelines on the management of pregnancies after liver transplantation. The aim of this position paper is to review the available evidence on pregnancy in liver transplant recipients and to provide national Italian recommendations for clinicians caring for these patients. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

IgG4-related disease is a rare inflammatory disorder that may mimic many infectious, malignant, and autoimmune conditions. The biliary tract is frequently involved, but hepatic lesions are rarely seen. Diagnosis is often delayed due to the absence of specific clinical and radiological signs, and the lack of an accurate diagnostic marker. Differential diagnosis includes cholangiocarcinoma, primary sclerosing cholangitis and intrinsic or metastatic liver disease. Corticosteroids are the cornerstone of therapy but treatment has not been standardized and relapse is common. Based on two cases of IgG4-related hepatobiliary disease, we review the current literature on this pathological entity.

The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Wait-listed (n = 226) or post-liver transplantation (n = 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (

Background and Aims: Chronic liver damage causes hepatic stellate cell activation and contraction, leading to intrahepatic microvascular and structural changes. Bosentan, an endothelin-1 receptor A and B antagonist, decreases portal pressure, however intrahepatic in vivo effects have never been studied. We will study the in vivo effects of bosentan on hepatic microcirculation in a mouse model of cirrhosis by measuring sinusoidal diameter with intravital fluorescence microscopy (IVFM). Methods: In male Swiss mice (n = 4) cirrhosis was induced by subcutaneous (SC) injection of carbon tetrachloride (CCl4, 1:1 in olive oil; 1 ml/kg) twice weekly for 16 weeks. Control mice (n = 4) received pure olive oil (1 ml/kg) SC. Hepatic microcirculation was visualised in vivo by IVFM after intravenous (IV) infusion of sodium fluorescein. Sinusoidal diameters were measured after 0, 5, 10, 15, 20, 25, 30, 45 and 60 min of a continuous IV infusion of 10 mg/kg/h bosentan or placebo. Results: Baseline sinusoidal diameter in CCl4 mice (5.9 mm ± 0.3) was significantly smaller than in control mice (6.7 mm ± 0.2) (PConclusions: Sinusoidal diameter in a cirrhotic mouse is significantly smaller than in a control mouse, which demonstrates in vivo the narrowing of liver sinusoids in a cirrhotic mouse model. Bosentan causes a significant sinusoidal vasodilation after 15 and 20 minutes of an IV administration in the CCl4 group. On the other hand, bosentan does not have an influence on liver sinusoids in the control group. These results demonstrate for the first time the in vivo vasodilatory effect of bosentan on liver sinusoids during cirrhosis, but there is tachyphylaxis after 20 minutes of IV infusion.

Background and study aims : The combination of Pegylated (PEG)interferon a-2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A : daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B : PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin ; Group C : interferon alfa-2b at a dose of 3 MIU TIW + ribavirin Patients and methods : Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A : daily interferon a-2b (4 MIU s.c. for patients > 65 kg or 0.06 MIU/kg 65 kg or 1.5 μg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm) : interferon a-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis ; 78 never started treatment (35 in group A, 28 in group B and 15 in group C) : 101 in group A, 98 in group B and 59 in group C. Results : Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38% of drop-outs were due to adverse events compared to 37% in group B and 58% in group C. No statistical differences were observed regarding safety. Conclusion : Daily weight based interferon a-2b dosing and PEG interferon a-2b weighed based dosing once weekly both in combination with Ribavirin offer the same efficacy and safety rates. (Acta gastro enterol. belg., 2008, 71, 293-297). Key words : chronic hepatitis C, interferon, daily administration, pegylated interferon.